The catecholamine neurons of the brain are known to be altered (l) by psychoactive drugs; (2) in certain behavioral states, including aggression and stress; and (3) in numerous psychotic and neurological disorders. Previous studies have shown that the noradrenergic neurons of the brain increase their rates of synthesis and utilization of the transmitter, norepinephrine (NE), during stress or oher altered behavioral state known to increase impulse flow in the NE neurons. Experiments in our laboratory have shown that the NE uptake mechanism, a mojor mode of inactivation of the released transmitter, is in a dynamic state that is readily, rapidly and reversibly altered by fighting, electroconvulsive shock, genetic hypertension or aggressiveness, and by acute stress. In this project we plan to study the dynamic changes in multiple neurochemical parameters in the NE nerve terminals of the rat brain, during increased or decreased impulse flow in the NE neurons. We will measure the activities of the major NE synthesizing and degradative enzymes, and the characteristics of storage, uptake and release of NE in the terminals. Decreased impulse flow will be achieved by acute lesioning of the cell bodies in the locus coeruleus, and increased impulse flow by subjecting the rats to a severe acute stress. In addition, a molecular pharmacological approach will be used to isolate and identify the NE uptake carrier in a purified nerve teminal membrane fraction of the cerebral cortex, in order to detect any changes in the carrier as a result of stress. Our studies are designed to form a broad base on which to build a better understanding of the regulatory sites responsible for altering the availability of transmitter during the dynamic state. Knowledge of the neurochemistry of the catecholamine neurons has led to major advances in the treatment of manic depressive illness, schizophrenia, Parkinson's disease, Huntington's disease and hypertension. Our studies should provide a more rational basis for treatment of these disorders, as well as gain new insight into how the organism lives and copes with stress.